Team: Rik van der Kant, Rob Wolthuis & Jan Koster

The project aims to accelerate both cancer and brain research using cutting-edge CRISPR technology. This initiative will integrate and innovate CRISPR applications in oncology and neuroscience by establishing a shared research infrastructure at Amsterdam UMC and identifying key targets for both neuro- and oncology drug development.

Key aspects of the project include:

• Interdisciplinary CRISPR Research: Dedicated researchers will collaborate with experts from oncology and neurology to optimize CRISPR technology in advanced cellular models, such as iPS cells, organoids and engineered cancer cell models, which better represent real disease processes than traditional cell lines.
• Living Stem Cell Library: This innovative resource will allow the generation of disease-relevant cell types that can be switched between healthy and diseased states, enabling direct comparison of genetic alterations in brain and tumor stem cells.
• CRISPR Screens for Therapeutic Targets: The project will conduct large-scale CRISPR screens to identify key genes involved in disease mechanisms and drug responses. In Alzheimer’s research, this will help understand how the ApoE4 gene contributes to harmful fat accumulation in brain cells. In oncology, CRISPR screens will uncover genes influencing cancer cell sensitizing and resistance mechanisms to new therapies, aiding in the development of targeted drug combinations. We will also screen the functional differences between relevant cancer-associated gene mutations, such as in BRCA1. We will further develop advanced flow-cytometry sorting based screens in neuro- and oncology based drug developments.
• Open Science & Data Sharing: Research findings will be made publicly accessible through an Amsterdam UMC platform, fostering collaboration beyond Adore and the Netherlands. We have started to generate a new website and tool for genome-wide screen data analysis. This will allow the integration with gene expression databases such as R2.

This project represents a major step toward precision medicine, accelerating discoveries and therapy development in neurodegeneration and cancer treatment.